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Evolutionary conservation between budding yeast and human kinetochores

Key Points

  • The kinetochore (centromere DNA and associated proteins) and its regulating system are essential for segregating chromosomes during mitosis.

  • The kinetochore provides the site of attachment to the mitotic spindle, and is also the site at which completion of metaphase is sensed by the cell-cycle regulatory machinery to coordinate the synchronous separation of chromosomes at the onset of anaphase. The kinetochore of yeast Saccharomyces cerevisiae is the best characterized.

  • This review describes the current state of knowledge of how the kinetochore is conserved between budding yeast and humans by looking at individual kinetochore components and considers them as three sets of subcomponents: first, the chromosomal DNA–inner kinetochore protein interface; second, the inner kinetochore–mitotic spindle interface; and last, the kinetochore protein–cell-cycle regulatory machinery interface.

  • The authors conclude that molecular understanding of the less complex budding yeast kinetochore provides an excellent framework for understanding the more complex kinetochores of humans. Furthermore, evidence indicates that the kinetochore and its regulating system are indeed highly conserved between budding yeast and humans, and research into the budding yeast should continue to reveal additional conserved functions at the kinetochore.

Abstract

Accurate chromosome segregation during mitosis requires the correct assembly of kinetochores — complexes of centromeric DNA and proteins that link chromosomes to spindle microtubules. Studies on the kinetochore of the budding yeast Saccharomyces cerevisiae have revealed functionally novel components of the kinetochore and its regulatory complexes, some of which are highly conserved in humans.

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Figure 1: Kinetochore function in budding yeast and mammals.
Figure 2: Kinetochore organization.
Figure 3: The DNA–inner kinetochore protein interface.
Figure 4: Kinetochore function and anaphase progression.

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DATABASE LINKS

Cbf1

Cse4

NDC10

CEP3

CTF13

SKP1

Sgt1

CENPA

CENPB

SKP1

SGT1

Mif2

Ctf19

Mcm21

Mtw1

CEN3

CEN15

Slk19

Plc1

KAR3

CIN8

phospholipase C

Bir1

Ndc80

Nuf2

Spc24

Spc25

Spc19

Spc34

Dam1

Stu2

Bik1

CENPC

CENPF

CENPE

MCAK

CLIP170

SUMO-1

Smt3

survivin

Mad1

Mad2

Mad3

Bub3

Cdc20

BUB1

MPS1

BUBR1

Smc1

Smc3

Scc1

Rec8

Esp1

Glossary

EUPLOIDY

An entire set of chromosomes is represented in integer increments (haploid, one set; diploid, two sets; triploid, three sets).

ALPHOID DNA

α-satellite DNA; highly repetitive satellite DNA.

SCF UBIQUITIN-LIGASE COMPLEX

An E3 enzyme that targets ubiquitin to cell-cycle-regulatory proteins (for example, Sic1, Clns), using an F-box protein as a specificity factor. SCF refers to 'Skp1/Cul1/F-box protein'.

CHIP

(in vivo crosslinking chromatin-immunoprecipitation methods). After live cells are chemically crosslinked, extracted and mechanically sheared, chromatin fragments (crosslinked DNA–protein complexes) are immunoprecipitated.

BIR MOTIF

A motif found in the 'inhibition of apoptosis' (IAP) proteins. It is essential for interaction of the IAP proteins with pro-apoptotic proteins, including the caspase family of death proteases.

RING-FINGER

A cysteine-rich zinc-binding domain, which is thought to be required for protein–protein interactions.

MIDBODY

Dense structure formed during cytokinesis at the cleavage furrow. It consists of remnants of spindle fibres and other amorphous material and disappears before cell division is completed.

NOCODAZOLE

A microtubule-depolymerizing drug.

ANEUPLOIDY

One or more chromosomes of a normal set of chromosomes are missing, or present in more than their usual number of copies.

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Kitagawa, K., Hieter, P. Evolutionary conservation between budding yeast and human kinetochores. Nat Rev Mol Cell Biol 2, 678–687 (2001). https://doi.org/10.1038/35089568

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  • DOI: https://doi.org/10.1038/35089568

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